Olfactory neurons have the unique ability to reinnervate the adult CNS in mammals. The replacement of olfactory neurons throughout life suggests that mechanisms used in development, turnover and post-lesion reinnervation are fundamentally similar. However, while neurogenesis and axon outgrowth may be similar in these three processes, the target-environment presented by the olfactory bulb in development, turnover and regeneration are profoundly different. Preliminary results from this laboratory, taken with other new findings, suggest that glial cells are fundamental to the composition of the target environment and play a critical role in the development of neural connections and the formation of local circuits. By contrast, adult glial cells react to injury/deafferentation and contribute to the hostile environment that prevents reinnervation. Since olfactory axons do successfully reinnervate the bulb, bulb astrocytes, olfactory neurons or both may have unique properties. LM-EM immunohistochemical studies will characterize the properties of olfactory neurons and glia and their interactions during development, following deafferentiation and during reinnervation. Neural transplantation experiments will be used to contrast neuron-glial interactions during development and reinnervation, test the ability of bulb astrocytes to support reinnervation by ectopic neurons and determine whether olfactory neurons can grow through or modify glial scars in the spinal cord. The goal of this research is to test novel hypotheses of the developmental and regenerative capacities of olfactory neurons and their interactions with olfactory glial cells. Understanding how olfactory neurons innervate the adult CNS may suggest new approaches for treating developmental disorders and provide new clues for promoting regenerative repair of the damaged brain.